Pharmacokinetics of o-nitroanisole in Fischer 344 rats
The pharmacokinetics and metabolism of o-nitroanisole (ONA) were studied in male Fischer 344 rats. Three dose levels of ( UC)ONA (5.0, 50, or 500 mg/kg) were administered orally to rats and daily excreta were analyzed for UC. Since the highest dose altered the urinary excretion rate of ONA, a dose of 25 mg/kg was used for subsequent pharmacokinetic studies. Following a single 25 mg/kg iv dose of ( UC)ONA, blood, tissues, and excreta were collected at times ranging from 15 min to 7 days. Urinary excretion accounted for 82% of the dose by 24 hr and 86% by 7 days. Fecal excretion was 7.5% in 24 hr and 9.0% by 7 days. Fifteen min after ONA administration, most of the UC content was found in muscle (20%), skin (10%), adipose tissue (6.8%), and blood (6.5%). The initial elimination t1/2 for UC in all tissues was 1-2 hr and the terminal t1/2 was approximately 4 days. The elimination of parent ONA from blood followed first order biphasic elimination kinetics. Parent ONA was rapidly eliminated from all other tissues in a monophasic manner. Skin and fat demonstrated an uptake phase prior to the elimination of parent. Only 0.5% of the dose was excreted as ONA in the urine. Urinary metabolites of ONA were predominantly conjugated compounds.
- Research Organization:
- Univ. of Arizona, Tucson
- OSTI ID:
- 6232425
- Journal Information:
- Drug Metab. Dispos.; (United States), Vol. 5
- Country of Publication:
- United States
- Language:
- English
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CARBON 14 COMPOUNDS
METABOLISM
PHARMACOLOGY
NITRO COMPOUNDS
ADIPOSE TISSUE
ANISOLE
BILE
BLOOD
FECES
HALF-LIFE
INTESTINAL ABSORPTION
KINETICS
MUSCLES
RATS
RETENTION
URINE
ABSORPTION
ANIMAL TISSUES
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CONNECTIVE TISSUE
ETHERS
LABELLED COMPOUNDS
MAMMALS
MATERIALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
RODENTS
TISSUES
UPTAKE
VERTEBRATES
WASTES
551001* - Physiological Systems- Tracer Techniques